As noted, 30+ other studies strongly indicate the merits of treating Covid-19 early with Hydroxychloroquine.
One notable study not on the list provides quantification and important wider context.
Accinelli et al, Hydroxychloroquine / azithromycin in COVID-19: The association between time to treatment and case fatality rate
https://www.sciencedirect.com/science/article/pii/S1477893921002040
Summary of importance
The Accinelli study has relevance as yet another basic hydroxychloroquine Covid-19 early treatment study.
So why is it not on the list? It’s because everyone in the study received HCQ.
It has much wider relevance because it studied the effect of the timing of the treatment. This led to outcomes that are (for many) surprising.
And the wider discussion indicates that the benefits of early treatment in Covid-19 could have been predicted by the research on Swine Flu, and are also supported by well-established research on early treatment for bacterial and fungal infections. In these related scenarios, early treatment is key.
Key findings from the Accinelli study
(i) The first significant finding was that earliness of the HCQ treatment for Covid-19 was not only a major factor in mortality, but was the most significant factor.
(ii) Also, early treatment with HCQ even eclipsed age in this study.
(iii) In fact, after the usual adjustments for the influential variables, age was not statistically significant. One should not get too carried away with this one fact, as age was nearly significant (the CI was [0.99 to 1.13], ie includes 1 but only just).
But for age to be even borderline is unusual – it is normally a highly significant factor.
(iv) Moreover, not only was age itself not significant after adjustment, but neither were any of the other variables – except the time to treatment itself.
Completing an existing picture – Swine flu studies
Unsurprisingly from a lay point of view, the need to treat serious infection early is not a new concept.
As noted in one of the papers cited in Accinelli (Kumar, ref[6]), this is well established for bacterial and fungal infections; it was less well recognized for viral infections – until the 2009 swine flu pandemic, according to Kumar, who writes: “Recently, following the 2009 swine flu pandemic, a large body of data regarding this issue became available. Studies analysing data from this pandemic have consistently shown that delays in initiation of antiviral therapy following symptom onset are significantly associated with disease severity and death. Optimal survival and minimal disease severity appear to result when antivirals are started as soon as possible after symptom onset.” https://academic.oup.com/jac/article/66/5/959/785705
The point is made just as unequivocally in the WHO Guidelines for Pharmacological Management of Pandemic Influenza A(H1N1) 2009 and Other Influenza Viruses.
Briefly, whatever the clinical presentation, the WHO guidance is to treat…as soon as possible – a phrase used six times in the opening summary table: https://www.ncbi.nlm.nih.gov/books/NBK138498/
In two of these swine flu studies cited in Accinelli, the odds ratios for mortality halved for patients treated early, while in a third study, a reduced interval from onset of symptoms to initiation of antiviral therapy was associated with reduced odds of admission to the ICU by a factor of 8.
Going back to Covid and hydroxychloroquine, the study by Kyung Soo Hong reported that administration of HCQ <5 days from diagnosis was the only protective factor for prolonging of viral shedding in COVID-19 patients. An interesting forerunner to (iv) above of Accinelli.
Kyung Soo Hong added: “Early administration of HCQ significantly ameliorates inflammatory cytokine secretion by eradicating COVID-19, at discharge. Our findings suggest that patients confirmed of COVID-19 infection should be administrated HCQ as soon as possible.”
Another study highlighted by Annicelli (ref [36]) did not report a positive effect from HCQ, though it contained a highly significant result in the subgroup pertaining to early treatment: whereas 139 (25.6%) of the 542 patients not treated with HCQ at all died, 67 were treated before admission and 2 (3%) died (see Table 2), a protective effect of 88%.
We leave the last word with Accinelli (who could reasonably have had all the words), who after discussing a further nine positive early-treatment HCQ covid-19 studies on our list, comments:
“So, all the studies with HCQ since the first week of symptoms in COVID-19 patients, including this, demonstrate protection for hospitalization and/or CFR“. That does say “all” (with apologies to Accinelli !)
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